Dataset Information

Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis.

ABSTRACT: MicroRNAs (miRNAs) are proposed as potential biomarkers for the diagnosis of numerous diseases. Here, we performed a meta-analysis to evaluate the utility of faecal miRNAs as a non-invasive tool in colorectal cancer (CRC) screening. A systematic literature search, according to predetermined criteria, in five databases identified 17 research articles including 6475, 783 and 5569 faecal-based miRNA tests in CRC, adenoma patients and healthy individuals, respectively. Sensitivity, specificity, positive/negative likelihood and diagnostic odds ratios, area under curve (AUC), summary receiver operator characteristic (sROC) curves, association of individual or combinations of miRNAs to cancer stage and location, subgroup, meta-regression and Deeks' funnel plot asymmetry analyses were employed. Pooled miRNAs for CRC had an AUC of 0.811, with a sensitivity of 58.8% (95% confidence interval [CI]: 51.7-65.5%) and specificity of 84.8% (95% CI: 81.1-87.8%), whilst for colonic adenoma, it was 0.747, 57.3% (95% CI: 40.8-72.3%) and 76.1% (95% CI: 66.1-89.4%), respectively. The most reliable individual miRNA was miR-21, with an AUC of 0.843, sensitivity of 59.3% (95% CI: 26.3-85.6%) and specificity of 85.6% (95% CI: 72.2-93.2%). Paired stage analysis showed a better diagnostic accuracy in late stage CRC and sensitivity higher in distal than proximal CRC. In conclusion, faecal miR-21, miR-92a and their combination are promising non-invasive biomarkers for faecal-based CRC screening.

SUBMITTER: Yau TO

PROVIDER: S-EPMC6603164 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis.

Yau Tung On TO Tang Ceen-Ming CM Harriss Elinor K EK Dickins Benjamin B Polytarchou Christos C

Scientific reports 20190701 1

MicroRNAs (miRNAs) are proposed as potential biomarkers for the diagnosis of numerous diseases. Here, we performed a meta-analysis to evaluate the utility of faecal miRNAs as a non-invasive tool in colorectal cancer (CRC) screening. A systematic literature search, according to predetermined criteria, in five databases identified 17 research articles including 6475, 783 and 5569 faecal-based miRNA tests in CRC, adenoma patients and healthy individuals, respectively. Sensitivity, specificity, posi ...[more]

PMID: 31263200

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Project description:Screening to detect colorectal cancer (CRC) in an early or premalignant state is an effective method to reduce CRC mortality rates. Current stool-based screening tests, e.g. fecal immunochemical test (FIT), have a suboptimal sensitivity for colorectal adenomas and difficulty distinguishing adenomas at high risk of progressing to cancer from those at lower risk. We aimed to identify stool protein biomarker panels that can be used for the early detection of high-risk adenomas and CRC. Proteomics data (LC-MS/MS) were collected on stool samples from adenoma (n = 71) and CRC patients (n = 81) as well as controls (n = 129). Colorectal adenoma tissue samples were characterized by low-coverage whole-genome sequencing to determine their risk of progression based on specific DNA copy number changes. Proteomics data were used for logistic regression modeling to establish protein biomarker panels. In total, 15 of the adenomas (15.8%) were defined as high risk of progressing to cancer. A protein panel, consisting of haptoglobin (Hp), LAMP1, SYNE2, and ANXA6, was identified for the detection of high-risk adenomas (sensitivity of 53% at specificity of 95%). Two panels, one consisting of Hp and LRG1 and one of Hp, LRG1, RBP4, and FN1, were identified for high-risk adenomas and CRCs detection (sensitivity of 66% and 62%, respectively, at specificity of 95%). Validation of Hp as a biomarker for high-risk adenomas and CRCs was performed using an antibody-based assay in FIT samples from a subset of individuals from the discovery series (n = 158) and an independent validation series (n = 795). Hp protein was significantly more abundant in high-risk adenoma FIT samples compared to controls in the discovery (p = 0.036) and the validation series (p = 9e-5). We conclude that Hp, LAMP1, SYNE2, LRG1, RBP4, FN1, and ANXA6 may be of value as stool biomarkers for early detection of high-risk adenomas and CRCs. © 2019 Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).

Dataset Information

Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis.

Publications

Faecal microRNAs as a non-invasive tool in the diagnosis of colonic adenomas and colorectal cancer: A meta-analysis.

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